Crosstalk between transcriptional control and energy pathways, mediated by hub metabolites

Scientific Research on Innovative Areas, a MEXT Grant-in-Aid Project FY2011-2015


Gene expression is regulated by a wide variety of factors in the nucleus, including genomic information encoded in the DNA, DNA methylation, chromatin-based epigenetic information (e.g., histone phosphorylation, acetylation, and methylation), and the activities of transcription factors. Via signal transduction pathways and nuclear complexes, this ‘transcriptional environment' is intimately involved in a range of cellular functions such as establishment of cell type—specific identity, growth, and differentiation. Cells maintain homeostasis and shift to a new steady state by controlling energy metabolism dynamically, in a manner that depends on growth state and stage of differentiation. Several intermediates of the glycolytic, TCA, methionine, and other major metabolic cycles (so-called ‘hub metabolites,' e.g., ATP, acetyl-CoA, S-adenosyl-L-methionine [SAM], NAD+, FAD, α-ketoglutarate) involved in energy regulation are recruited for the formation of the transcriptional environment.

In order to better understand the crosstalk regulation between the transcriptional environment and energy metabolism, our research focuses on intracellular mechanisms such as epigenetic modification by modification enzymes (‘writing'), adaptor molecule—mediated recognition of these modifications (‘reading'), removal of modifications by enzymes such as demethylases and deacetylases (‘erasing'), and chromatin repair (‘rewriting'). By studying these processes, we can explore the transcriptional and metabolic systems involved in the formation of complex networks and the regulation of target gene expression. Our primary goal is to clarify the effects of the transcriptional environment on metabolic behavior, and how the metabolic changes induced by external and internal stimuli influence the formation of the transcriptional environment.